1. Field of the Invention
The present invention relates generally to sapphyrin compounds, and particularly, to water-soluble sapphyrin derivatives. Water-soluble sapphyrins include sapphyrins having hydroxy, hydroxyalkyl, oxyalkyl, carboxyamide, polyhydroxy or carbohydrate substituents, for example; and are useful for transport, drug delivery, DNA binding, photodynamic therapy and DNA cleavage.
2. Description of the Related Art
Sapphyrins are large pyrrole-containing macrocyclic analogues of the porphyrins. A number of expanded porphyrin systems are now known. However, only a few fully conjugated examples have been reported that contain more that four pyrrolic subunits, namely the smaragdyrins, sapphyrins, pentaphyrins, hexaphyrins, and superphthalocyanines among others..sup.1 Sapphyrin, in its generalized substituent-free form, is represented by structure I. ##STR1##
Sapphyrin, first discovered serendipitously by Woodward.sup.2 is one of the more intriguing products to emerge from initial studies directed towards the synthesis of Vitamin B.sub.12..sup.2,3 It is a 22 pi-electron pentapyrrolic macrocycle which exhibits an intense Soret-like band at about 450 nm (CHCl.sub.3) along with weaker Q-type transitions in the 620 to 690 nm region. These optical properties, along with the presence of a large central cavity which could serve for metal binding, renders sapphyrin useful for certain biomedical applications, including photodynamic therapy (PDT).
In addition to the above, certain expanded porphyrins, including especially those of the sapphyrin series, have been found to act as halide anion chelating agents in both solution and the solid state.sup.4.
Unfortunately, all sapphyrins known at the time of this invention were essentially insoluble in water and were all of such simple character in terms of peripheral substituents, that only those bearing hydrogen or alkyl were known.sup.2,3. These two deficiencies limited the potential utility of sapphyrins for any applications associated with their use at or near neutral pH and, more generally, any conditions involving partial or complete association with an aqueous environment.
Furthermore, it was recognized that the synthesis of one or more water-soluble sapphyrins would represent a considerable advantage, not only in terms of anion recognition and transport, but also because it would allow for a detailed study of the basic binding phenomena in aqueous media. This latter would be particular true if said water-soluble sapphyrin were neutral in character.
There still remains considerable scope for the design of improved chemotherapeutic compounds which act upon DNA once inside a target cell. Since currently available chemotherapeutic agents have complex structures, or complicated modes of interaction with their targets that preclude systematic improvement, the development of a novel class of DNA binding compounds would open up new avenues for the design of improved therapeutics. In this regard, a class of compounds that can be modified in a number of different ways whilst maintaining their overall structure would be particularly advantageous. The same is true for compounds that can be activated by light, or other means, to produce singlet oxygen or hydroxyl radicals, once bound to DNA. These considerations provided the present inventors with further impetus for the design and synthesis of improved sapphyrins such as those embodied by the present invention.